YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
総説
免疫抑制剤の体内動態と薬効の速度論的解析に基づく個別化投与設計に関する研究
福土 将秀
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ジャーナル フリー

2007 年 127 巻 7 号 p. 1081-1089

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  The calcineurin inhibitors cyclosporine and tacrolimus are widely used to prevent allograft rejection after transplantation. Since these drugs have narrow therapeutic windows and show considerable pharmacokinetic variability, therapeutic drug monitoring (TDM) is essential to avoid adverse effects such as nephrotoxicity while maximizing immunosuppressive efficacy. On the other hand, some patients experience acute rejection episodes or postoperative complications despite achieving therapeutic blood drug levels. Therefore, pharmacokinetic and pharmacodynamic factors by which to establish individualized dosage adjustment for these drugs should be identified. Recently, it was recognized that pharmacogenomics has the potential to facilitate personalized medicine by translating knowledge of human genome variability into rational therapeutics. In this paper, we review the population pharmacokinetic and pharmacogenomic analysis of tacrolimus, focusing on an efflux transporter P-glycoprotein (multidrug resistance 1 [MDR1/ABCB1]) and drug-metabolizing enzymes cytochrome P450 (CYP) 3A4 and 3A5, and describe Bayesian forecasting to individualize the tacrolimus dose in de novo living-donor liver transplant recipients. Furthermore, the pharmacodynamic properties of tacrolimus and cyclosporine, which were evaluated by measuring calcineurin phosphatase activity in peripheral blood mononuclear cells, are reviewed in relation to an optimal monitoring strategy as well as a rational dosage regimen for these drugs.

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© 2007 by the PHARMACEUTICAL SOCIETY OF JAPAN
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